tbuckley/cabot-search huggingface dataset:
The clinical imperative of a complete biochemical response to immunosuppression in autoimmune hepatitis: Close is not good enough!
Authors: George Cholankeril, John M. Vierling
Journal: Hepatology (2023)

Section of Gastroenterology and Hepatology, Margaret M. and Albert B. Alkek Department of Medicine and Division of Abdominal Transplantation, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas Abbreviations: AIH, autoimmune hepatitis; ALT, alanine transaminase; CBR, complete biochemical response; CR, complete remission defined by both biochemical and histological criteria; IAIHG, International Autoimmune Hepatitis Group; LT, liver transplantation; PBC, primary biliary cholangitis; PSC, primary sclerosing cholangitis; UK, United Kingdom. Correspondence John M. Vierling, Professor of Medicine and Surgery, Baylor College of Medicine. Email: [email protected]
Forgiving Physician Debt
Authors: Laura C. Hart
Journal: Annals of Internal Medicine (2023)

LettersSeptember 2023Forgiving Physician DebtLaura C. Hart, MD, MPHLaura C. Hart, MD, MPHNationwide Children's Hospital and The Ohio State University, Columbus, OhioSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L23-0226 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR: I read Grischkan and Asch's commentary (1) with interest. As someone who recently received forgiveness through the Public Service Loan Forgiveness Program, I can confidently say that the process has improved tremendously in the past few years. Although some of that improvement can be attributed to the current administration, I believe we also need to consider that it took us 10 years (that is, until 2017) to figure out what the issues were and then a few more to iron those issues out.I am concerned that the authors' suggestion of forgiving debt annually would mean that ...Reference1. Grischkan JA, Asch DA. Forgiving physician debt [Editorial]. Ann Intern Med. 2023;176:406-407. [PMID: 36780648] doi:10.7326/M22-2832 LinkGoogle Scholar Author, Article, and Disclosure InformationAuthors: Laura C. Hart, MD, MPHAffiliations: Nationwide Children's Hospital and The Ohio State University, Columbus, OhioDisclosures: Authors have reported no disclosures of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=L23-0226. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Current IssueSeptember 2023Volume 176, Issue 9KeywordsGraduate medical educationHealth careMedical educationMotivationPublic policyResidency ePublished: 19 September 2023 Issue Published: September 2023 Copyright & PermissionsCopyright © 2023 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Inaugural Results of the Individualized Screening Trial of Innovative Glioblastoma Therapy: A Phase II Platform Trial for Newly Diagnosed Glioblastoma Using Bayesian Adaptive Randomization
Authors: Rifaquat Rahman, Lorenzo Trippa, Eudocia Q. Lee, Isabel Arrillaga-Romany, Geoffrey Fell, Mehdi Touat, Christine McCluskey, Jennifer Wiley, Sarah Gaffey, Jan Drappatz, Mary R. Welch, Evanthia Galanis, Manmeet S. Ahluwalia, Howard Colman, L. Burt Nabors, Jaroslaw Hepel, Heinrich Elinzano, David Schiff, Ugonma N. Chukwueke, Rameen Beroukhim, Lakshmi Nayak, J. Ricardo McFaline-Figueroa, Tracy T. Batchelor, Mikael L. Rinne, Thomas J. Kaley, Christine Lu-Emerson, Ingo K. Mellinghoff, Wenya Linda Bi, Omar Arnaout, Pier Paolo Peruzzi, Daphne Haas-Kogan, Shyam Tanguturi, Daniel Cagney, Ayal Aizer, Lisa Doherty, Maria Lavallee, Brittany Fisher-Longden, Shanna Dowling, Jack Geduldig, Fiona Watkinson, William Pisano, Seth Malinowski, Shakti Ramkissoon, Sandro Santagata, David M. Meredith, E. Antonio Chiocca, David A. Reardon, Brian M. Alexander, Keith L. Ligon, Patrick Y. Wen
Journal: Journal of Clinical Oncology (2023)

The Individualized Screening Trial of Innovative Glioblastoma Therapy (INSIGhT) is a phase II platform trial that uses response adaptive randomization and genomic profiling to efficiently identify novel therapies for phase III testing. Three initial experimental arms (abemaciclib [a cyclin-dependent kinase [CDK]4/6 inhibitor], neratinib [an epidermal growth factor receptor [EGFR]/human epidermal growth factor receptor 2 inhibitor], and CC-115 [a deoxyribonucleic acid-dependent protein kinase/mammalian target of rapamycin inhibitor]) were simultaneously evaluated against a common control arm. We report the results for each arm and examine the feasibility and conduct of the adaptive platform design.
Impact of Socioeconomic Background on Cardiovascular Health Promotion in Early Childhood
Authors: Amaya de Cos-Gandoy, Gloria Santos-Beneit, Patricia Bodega, Jorge Baxter, Raquel Diaz-Munoz, Christopher A. Hill, Isabel Carvajal, Carlos Peyra, Rodrigo Fernandez-Jimenez, Valentin Fuster
Journal: Journal of the American College of Cardiology (2023)
Response by Essayagh et al to Letter Regarding Article, “The MIDA-Q Mortality Risk Score: A Quantitative Prognostic Tool for the Mitral Valve Prolapse Spectrum”
Authors: Benjamin Essayagh, Giovanni Benfari, Clemence Antoine, Francesco Grigioni, Thierry Le Tourneau, Jean-Christian Roussel, Jeroen J. Bax, Nina Ajmone Marsan, Aniek van Wijngaarden, Christophe Tribouilloy, Dan Rusinaru, Aviram Hochstadt, Yan Topilsky, Prabin Thapa, Hector I. Michelena, Maurice Enriquez-Sarano
Journal: Circulation (2023)
Improved phenotypic classification of male infertility to promote discovery of genetic causes
Authors: Margot J. Wyrwoll, Godfried W. van der Heijden, Csilla Krausz, Kenneth I. Aston, Sabine Kliesch, Robert McLachlan, Liliana Ramos, Donald F. Conrad, Moira K. O’Bryan, Joris A. Veltman, Frank Tüttelmann
Journal: Nature Reviews Urology (2023)
Impact of taxes and warning labels on red meat purchases among US consumers: A randomized controlled trial
Authors: Lindsey Smith Taillie, Maxime Bercholz, Carmen E. Prestemon, Isabella C. A. Higgins, Anna H. Grummon, Marissa G. Hall, Lindsay M. Jaacks
Journal: PLoS Medicine (2023)

Policies to reduce red meat intake are important for mitigating climate change and improving public health. We tested the impact of taxes and warning labels on red meat purchases in the United States. The main study question was, will taxes and warning labels reduce red meat purchases?
We must confront sexual violence in the NHS to prevent further institutional harm
Authors: Philippa Greenfield
Journal: BMJ (2023)

We must confront sexual violence in the NHS to prevent further institutional harm Extensive cultural change is needed in the NHS to tackle sexual violence and prevent further institutional harm to patients and staff, writes Philippa Greenfield Philippa Greenfield co-presidential lead for women and mental health, consultant general adult psychiatrist, named doctor for adult safeguarding and trauma informed lead
HPC-Atlas: Computationally Constructing a Comprehensive Atlas of Human Protein Complexes
Authors: Yuliang Pan, Ruiyi Li, Wengen Li, Liuzhenghao Lv, Jihong Guan, Shuigeng Zhou
Journal: Genomics Proteomics & Bioinformatics (2023)

A fundamental principle of biology is that proteins tend to form complexes to play important roles in the core functions of cells. For a complete understanding of human cellular functions, it is crucial to have a comprehensive atlas of human protein complexes. Unfortunately, we still lack such a comprehensive atlas of experimentally validated protein complexes, which prevents us from gaining a complete understanding of the compositions and functions of human protein complexes, as well as the underlying biological mechanisms. To fill this gap, we built Human Protein Complexes Atlas (HPC-Atlas), as far as we know, the most accurate and comprehensive atlas of human protein complexes available to date. We integrated two latest protein interaction networks, and developed a novel computational method to identify nearly 9000 protein complexes, including many previously uncharacterized complexes. Compared with the existing methods, our method achieved outstanding performance on both testing and independent datasets. Furthermore, with HPC-Atlas we identified 751 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-affected human protein complexes, and 456 multifunctional proteins that contain many potential moonlighting proteins. These results suggest that HPC-Atlas can serve as not only a computing framework to effectively identify biologically meaningful protein complexes by integrating multiple protein data sources, but also a valuable resource for exploring new biological findings. The HPC-Atlas webserver is freely available at http://www.yulpan.top/HPC-Atlas.
Identification of novel genetic loci for risk of multiple myeloma by functional annotation
Authors: Angelica Macauda, Klara Briem, Alyssa Clay-Gilmour, Wendy Cozen, Asta Försti, Matteo Giaccherini, Chiara Corradi, Juan Sainz, Yasmeen Niazi, Rob ter Horst, Yang Li, Mihai G. Netea, Ulla Vogel, Kari Hemminki, Susan L. Slager, Judit Varkonyi, Vibeke Andersen, Elzbieta Iskierka-Jazdzewska, Joaquin Mártinez-Lopez, Jan Zaucha, Nicola J. Camp, S. Vincent Rajkumar, Agnieszka Druzd-Sitek, Parveen Bhatti, Stephen J. Chanock, Shaji K. Kumar, Edyta Subocz, Grzegorz Mazur, Stefano Landi, Mitchell J. Machiela, Andrés Jerez, Aaron D. Norman, Michelle A. T. Hildebrandt, Katalin Kadar, Sonja I. Berndt, Elad Ziv, Gabriele Buda, Arnon Nagler, Charles Dumontet, Malgorzata Raźny, Marzena Watek, Aleksandra Butrym, Norbert Grzasko, Marek Dudzinski, Malwina Rybicka-Ramos, Eva-Laure Matera, Ramón García-Sanz, Hartmut Goldschmidt, Krzysztof Jamroziak, Artur Jurczyszyn, Esther Clavero, Graham G. Giles, Matteo Pelosini, Daria Zawirska, Marcin Kruszewski, Herlander Marques, Eva Haastrup, José Manuel Sánchez-Maldonado, Uta Bertsch, Marcin Rymko, Marc-Steffen Raab, Elizabeth E. Brown, Jonathan N. Hofmann, Celine Vachon, Daniele Campa, Federico Canzian
Journal: Leukemia (2023)
GAMMA challenge: Glaucoma grAding from Multi-Modality imAges
Authors: Junde Wu, Huihui Fang, Fei Li, Huazhu Fu, Fengbin Lin, Jiongcheng Li, Yue Huang, Qinji Yu, Sifan Song, Xinxing Xu, Yanyu Xu, Wensai Wang, Lingxiao Wang, Shuai Lu, Huiqi Li, Shihua Huang, Zhichao Lu, Chubin Ou, Xifei Wei, Bingyuan Liu, Riadh Kobbi, Xiaoying Tang, Li Lin, Qiang Zhou, Qiang Hu, Hrvoje Bogunović, José Ignacio Orlando, Xiulan Zhang, Yanwu Xu
Journal: Medical Image Analysis (2023)
GLUT3 promotes macrophage signaling and function via RAS-mediated endocytosis in atopic dermatitis and wound healing
Authors: Dong-Min Yu, Jiawei Zhao, Eunice E. Lee, Dohun Kim, Ruchika Mahapatra, Elysha K. Rose, Zhiwei Zhou, Calvin Hosler, Abdullah El Kurdi, Jun-Yong Choe, E. Dale Abel, Gerta Hoxhaj, Kenneth D. Westover, Raymond J. Cho, Jeffrey B. Cheng, Richard C. Wang
Journal: Journal of Clinical Investigation (2023)

The facilitative GLUT1 and GLUT3 hexose transporters are expressed abundantly in macrophages, but whether they have distinct functions remains unclear. We confirmed that GLUT1 expression increased after M1 polarization stimuli and found that GLUT3 expression increased after M2 stimulation in macrophages. Conditional deletion of Glut3 (LysM-Cre Glut3fl/fl) impaired M2 polarization of bone marrow-derived macrophages. Alternatively activated macrophages from the skin of patients with atopic dermatitis showed increased GLUT3 expression, and a calcipotriol-induced model of atopic dermatitis was rescued in LysM-Cre Glut3fl/fl mice. M2-like macrophages expressed GLUT3 in human wound tissues as assessed by transcriptomics and costaining, and GLUT3 expression was significantly decreased in nonhealing, compared with healing, diabetic foot ulcers. In an excisional wound healing model, LysM-Cre Glut3fl/fl mice showed significantly impaired M2 macrophage polarization and delayed wound healing. GLUT3 promoted IL-4/STAT6 signaling, independently of its glucose transport activity. Unlike plasma membrane-localized GLUT1, GLUT3 was localized primarily to endosomes and was required for the efficient endocytosis of IL-4Rα subunits. GLUT3 interacted directly with GTP-bound RAS in vitro and in vivo through its intracytoplasmic loop domain, and this interaction was required for efficient STAT6 activation and M2 polarization. PAK activation and macropinocytosis were also impaired without GLUT3, suggesting broader roles for GLUT3 in the regulation of endocytosis. Thus, GLUT3 is required for efficient alternative macrophage polarization and function, through a glucose transport-independent, RAS-mediated role in the regulation of endocytosis and IL-4/STAT6 activation.
Boosting the power of genome-wide association studies within and across ancestries by using polygenic scores
Authors: Adrian I. Campos, Shinichi Namba, Shu-Chin Lin, Kisung Nam, Julia Sidorenko, Huanwei Wang, Yoichiro Kamatani, Ling-Hua Wang, Seunggeun Lee, Yen-Feng Lin, Yen-Chen Anne Feng, Yukinori Okada, Peter M. Visscher, Loic Yengo
Journal: Nature Genetics (2023)
Molecular basis for maternal inheritance of human mitochondrial DNA
Authors: William Lee, Angelica Zamudio-Ochoa, Gina Buchel, Petar Podlesniy, Nuria Marti Gutierrez, Margalida Puigròs, Anna Calderon, Hsin-Yao Tang, Li Li, Aleksei Mikhalchenko, Amy Koski, Ramon Trullas, Shoukhrat Mitalipov, Dmitry Temiakov
Journal: Nature Genetics (2023)
Adaptor protein AP-3 produces synaptic vesicles that release at high frequency by recruiting phospholipid flippase ATP8A1
Authors: Hongfei Xu, Juan A. Oses-Prieto, Mikhail Khvotchev, Shweta Jain, Jocelyn Liang, Alma Burlingame, Robert H. Edwards
Journal: Nature Neuroscience (2023)
Longitudinal genomic surveillance of carriage and transmission of Clostridioides difficile in an intensive care unit
Authors: Arianna Miles-Jay, Evan S. Snitkin, Michael Y. Lin, Teppei Shimasaki, Michael Schoeny, Christine Fukuda, Thelma Dangana, Nicholas Moore, Sarah E. Sansom, Rachel D. Yelin, Pamela Bell, Krishna Rao, Micah Keidan, Alexandra Standke, Christine Bassis, Mary K. Hayden, Vincent B. Young
Journal: Nature Medicine (2023)

Abstract Despite enhanced infection prevention efforts, Clostridioides difficile remains the leading cause of healthcare-associated infections in the United States. Current prevention strategies are limited by their failure to account for patients who carry C. difficile asymptomatically, who may act as hidden reservoirs transmitting infections to other patients. To improve the understanding of asymptomatic carriers’ contribution to C. difficile spread, we conducted admission and daily longitudinal culture-based screening for C. difficile in a US-based intensive care unit over nine months and performed whole-genome sequencing on all recovered isolates. Despite a high burden of carriage, with 9.3% of admissions having toxigenic C. difficile detected in at least one sample, only 1% of patients culturing negative on admission to the unit acquired C. difficile via cross-transmission. While patients who carried toxigenic C. difficile on admission posed minimal risk to others, they themselves had a 24-times greater risk for developing a healthcare-onset C. difficile infection than noncarriers. Together, these findings suggest that current infection prevention practices can be effective in preventing nosocomial cross-transmission of C. difficile , and that decreasing C. difficile infections in hospitals further will require interventions targeting the transition from asymptomatic carriage to infection.
Acetate acts as a metabolic immunomodulator by bolstering T-cell effector function and potentiating antitumor immunity in breast cancer
Authors: Katelyn D. Miller, Seamus O’Connor, Katherine A. Pniewski, Toshitha Kannan, Reyes Acosta, Gauri Mirji, Sara Papp, Michael Hulse, Dzmitry Mukha, Sabina I. Hlavaty, Kelsey N. Salcido, Fabrizio Bertolazzi, Yellamelli V. V. Srikanth, Steven Zhao, Kathryn E. Wellen, Rahul S. Shinde, Daniel T. Claiborne, Andrew Kossenkov, Joseph M. Salvino, Zachary T. Schug
Journal: Nature Cancer (2023)
PD-1 instructs a tumor-suppressive metabolic program that restricts glycolysis and restrains AP-1 activity in T cell lymphoma
Authors: Tim Wartewig, Jay Daniels, Miriam Schulz, Erik Hameister, Abhinav Joshi, Joonhee Park, Emma Morrish, Anuroop V. Venkatasubramani, Filippo M. Cernilogar, Frits H. A. van Heijster, Christian Hundshammer, Heike Schneider, Filippos Konstantinidis, Judith V. Gabler, Christine Klement, Henry Kurniawan, Calvin Law, Yujin Lee, Sara Choi, Joan Guitart, Ignasi Forne, Jérôme Giustinani, Markus Müschen, Salvia Jain, David M. Weinstock, Roland Rad, Nicolas Ortonne, Franz Schilling, Gunnar Schotta, Axel Imhof, Dirk Brenner, Jaehyuk Choi, Jürgen Ruland
Journal: Nature Cancer (2023)

Abstract The PDCD1 -encoded immune checkpoint receptor PD-1 is a key tumor suppressor in T cells that is recurrently inactivated in T cell non-Hodgkin lymphomas (T-NHLs). The highest frequencies of PDCD1 deletions are detected in advanced disease, predicting inferior prognosis. However, the tumor-suppressive mechanisms of PD-1 signaling remain unknown. Here, using tractable mouse models for T-NHL and primary patient samples, we demonstrate that PD-1 signaling suppresses T cell malignancy by restricting glycolytic energy and acetyl coenzyme A (CoA) production. In addition, PD-1 inactivation enforces ATP citrate lyase (ACLY) activity, which generates extramitochondrial acetyl-CoA for histone acetylation to enable hyperactivity of activating protein 1 (AP-1) transcription factors. Conversely, pharmacological ACLY inhibition impedes aberrant AP-1 signaling in PD-1-deficient T-NHLs and is toxic to these cancers. Our data uncover genotype-specific vulnerabilities in PDCD1 -mutated T-NHL and identify PD-1 as regulator of AP-1 activity.
Nuclear envelope disruption triggers hallmarks of aging in lung alveolar macrophages
Authors: Nilushi S. De Silva, Johan Siewiera, Chantal Alkhoury, Guilherme P. F. Nader, Francesca Nadalin, Kevin de Azevedo, Mickaël Couty, Helena M. Izquierdo, Anvita Bhargava, Cécile Conrad, Mathieu Maurin, Konstantina Antoniadou, Charles Fouillade, Arturo Londono-Vallejo, Rayk Behrendt, Karine Bertotti, Cindy Serdjebi, François Lanthiez, Lisa Gallwitz, Paul Saftig, Beatriz Herrero-Fernández, Angela Saez, José María González-Granado, Guillaume van Niel, Alexandre Boissonnas, Matthieu Piel, Nicolas Manel
Journal: Nature Aging (2023)
DOPA decarboxylase is an emerging biomarker for Parkinsonian disorders including preclinical Lewy body disease
Authors: Joana B. Pereira, Atul Kumar, Sara Hall, Sebastian Palmqvist, Erik Stomrud, Divya Bali, Piero Parchi, Niklas Mattsson-Carlgren, Shorena Janelidze, Oskar Hansson
Journal: Nature Aging (2023)

Abstract The diagnosis of Parkinsonian disorders is currently based on clinical criteria, which have limited sensitivity until most dopaminergic neurons are lost. Here we show that cerebrospinal fluid levels of DOPA decarboxylase (DDC) (also known as aromatic l -amino acid decarboxylase) can accurately identify patients with Lewy body disease (LBD) (area under the curve (AUC) = 0.89; P FDR = 2.6 × 10 −13 ) and are associated with worse cognitive performance ( P &lt; 0.05). We also found that DDC can detect preclinical LBD stages in clinically unimpaired individuals with a positive seed amplification α-synuclein assay (AUC = 0.81, P = 1.0 × 10 −5 ) and that this biomarker could predict progression to clinical LBD over a 3-year period in preclinical cases (hazard ratio = 3.7 per s.d. change, confidence interval = 1.1–12.7). Moreover, DDC levels were also increased in atypical Parkinsonian disorders but not in non-Parkinsonian neurodegenerative disorders. These cerebrospinal fluid results were replicated in an independent cohort, where we also found that DDC levels in plasma could identify both LBD and atypical Parkinsonian disorders (AUC = 0.92, P = 1.3 × 10 −14 ). Our results show that DDC might have a future role in clinical practice as a biomarker of dopaminergic dysfunction to detect Parkinsonian disorders even during the preclinical disease stages and predict their progression to clinical LBD.
IκBζ is an essential mediator of immunity to oropharyngeal candidiasis
Authors: Tiffany C. Taylor, Bianca M. Coleman, Samyuktha P. Arunkumar, Ipsita Dey, John T. Dillon, Nicole O. Ponde, Amanda C. Poholek, Daniella M. Schwartz, Mandy J. McGeachy, Heather R. Conti, Sarah L. Gaffen
Journal: Cell Host & Microbe (2023)
A view-based decision mechanism for rewards in the primate amygdala
Authors: Fabian Grabenhorst, Adrián Ponce-Alvarez, Alexandra Battaglia-Mayer, Gustavo Deco, Wolfram Schultz
Journal: Neuron (2023)

Primates make decisions visually by shifting their view from one object to the next, comparing values between objects, and choosing the best reward, even before acting. Here, we show that when monkeys make value-guided choices, amygdala neurons encode their decisions in an abstract, purely internal representation defined by the monkey's current view but not by specific object or reward properties. Across amygdala subdivisions, recorded activity patterns evolved gradually from an object-specific value code to a transient, object-independent code in which currently viewed and last-viewed objects competed to reflect the emerging view-based choice. Using neural-network modeling, we identified a sequence of computations by which amygdala neurons implemented view-based decision making and eventually recovered the chosen object's identity when the monkeys acted on their choice. These findings reveal a neural mechanism in the amygdala that derives object choices from abstract, view-based computations, suggesting an efficient solution for decision problems with many objects.
Three-dimensional reconstructions of mechanosensory end organs suggest a unifying mechanism underlying dynamic, light touch
Authors: Annie Handler, Qiyu Zhang, Song Pang, Tri M. Nguyen, Michael Iskols, Michael Nolan-Tamariz, Stuart Cattel, Rebecca Plumb, Brianna Sanchez, Karyl Ashjian, Aria Shotland, Bartianna Brown, Madiha Kabeer, Josef Turecek, Michelle M. DeLisle, Genelle Rankin, Wangchu Xiang, Elisa C. Pavarino, Nusrat Africawala, Celine Santiago, Wei-Chung Allen Lee, C. Shan Xu, David D. Ginty
Journal: Neuron (2023)

Across mammalian skin, structurally complex and diverse mechanosensory end organs respond to mechanical stimuli and enable our perception of dynamic, light touch. How forces act on morphologically dissimilar mechanosensory end organs of the skin to gate the requisite mechanotransduction channel Piezo2 and excite mechanosensory neurons is not understood. Here, we report high-resolution reconstructions of the hair follicle lanceolate complex, Meissner corpuscle, and Pacinian corpuscle and the subcellular distribution of Piezo2 within them. Across all three end organs, Piezo2 is restricted to the sensory axon membrane, including axon protrusions that extend from the axon body. These protrusions, which are numerous and elaborate extensively within the end organs, tether the axon to resident non-neuronal cells via adherens junctions. These findings support a unified model for dynamic touch in which mechanical stimuli stretch hundreds to thousands of axon protrusions across an end organ, opening proximal, axonal Piezo2 channels and exciting the neuron.